1 Department of Neurology, Academic Medical Center , Amsterdam, the Netherlands .
J Neurotrauma. 2013 Dec 15;30(24):2073-9. doi: 10.1089/neu.2013.3060. Epub 2013 Oct 24.
Traumatic brain injury (TBI) is frequently complicated by acute lung injury, which is predictive for poor outcome. However, it is unclear whether lung injury develops independently or as a result of mechanical ventilation after TBI. Further, TBI is strongly associated with the development of pneumonia, suggesting a specific vulnerability for the development of nosocomial infections in the lung after TBI. In this study, we evaluated whether indeed pulmonary injury and immune suppression develop spontaneously in an animal model of mild TBI (mTBI). TBI was induced in male PVG rats by closed-head trauma using a weight-drop device. Subsequently, we evaluated the effects of this on the lungs as well as on the excitability of the systemic immune system. Finally, we performed an experiment in which TBI was followed by induction of pneumonitis and evaluated whether TBI affects the severity of subsequent pneumonitis induced by intratracheal instillation of heat-killed Staphylococcus aureus. mTBI resulted in significant lung injury, as evidenced by pulmonary edema, protein leakage to the alveolar compartment, and increased concentrations of interleukin-1 and -6 in broncho alveolar lavage fluid (all p<0.05 vs. sham-treated animals). Further, after TBI, the release of tumor necrosis factor alpha was decreased when whole blood was stimulated ex vivo (p<0.05 TBI vs. sham), indicating systemic immune suppression. When TBI was followed by pneumonitis, the severity of subsequent pneumonitis was not different in rats previously subjected to TBI or sham treatment (p>0.05), suggesting that systemic immune suppression is not translated toward the pulmonary compartment in this specific model. We here show that during mild experimental TBI, acute pulmonary injury, as well as a decrease in the excitability of the systemic immune system, can be observed.
创伤性脑损伤（TBI）常伴有急性肺损伤，后者是预后不良的预测因素。然而，目前尚不清楚肺损伤是独立发生还是 TBI 后机械通气的结果。此外，TBI 与肺炎的发生密切相关，这表明 TBI 后肺部发生医院获得性感染具有特定的易感性。在这项研究中，我们评估了轻度 TBI（mTBI）动物模型中肺损伤和免疫抑制是否确实自发发生。使用重物下落装置对雄性 PVG 大鼠进行闭合性颅脑创伤以诱导 TBI。随后，我们评估了这对肺部以及全身免疫系统兴奋性的影响。最后，我们进行了一项实验，其中 TBI 后诱导肺炎，并评估 TBI 是否影响经气管内滴注热灭活金黄色葡萄球菌诱导的随后肺炎的严重程度。mTBI 导致明显的肺损伤，如肺水肿、肺泡腔蛋白渗漏和支气管肺泡灌洗液中白细胞介素-1 和 -6 浓度增加（均 p<0.05 与假手术处理动物相比）。此外，TBI 后，当全血在体外刺激时，肿瘤坏死因子-α的释放减少（p<0.05 TBI 与假手术相比），表明全身免疫抑制。当 TBI 后发生肺炎时，先前接受 TBI 或假手术处理的大鼠随后发生肺炎的严重程度没有差异（p>0.05），这表明在这种特定模型中，全身免疫抑制不会向肺部转移。我们在这里表明，在轻度实验性 TBI 期间，可观察到急性肺损伤以及全身免疫系统兴奋性降低。
